4-Methylmorpholine → (S)-1-((4-(2,5-difluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-yl)amino)-1-oxopropan-2-yl acetate

HRID 476388Notes

Reaction equation

[C:1]([O:4][C@@H:5]([CH3:9])[C:6]([OH:8])=O)(=[O:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[NH2:25][C:26]1[CH:31]=[C:30]([O:32][C:33]2[C:38]([F:39])=[CH:37][C:36]([NH:40][C:41]([C:43]3([C:46]([NH:48][C:49]4[CH:54]=[CH:53][C:52]([F:55])=[CH:51][CH:50]=4)=[O:47])[CH2:45][CH2:44]3)=[O:42])=[C:35]([F:56])[CH:34]=2)[CH:29]=[CH:28][N:27]=1>C(Cl)Cl>[C:1]([O:4][C@@H:5]([CH3:9])[C:6]([NH:25][C:26]1[CH:31]=[C:30]([O:32][C:33]2[CH:34]=[C:35]([F:56])[C:36]([NH:40][C:41]([C:43]3([C:46](=[O:47])[NH:48][C:49]4[CH:50]=[CH:51][C:52]([F:55])=[CH:53][CH:54]=4)[CH2:45][CH2:44]3)=[O:42])=[CH:37][C:38]=2[F:39])[CH:29]=[CH:28][N:27]=1)=[O:8])(=[O:3])[CH3:2]

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of (S)-2-Acetoxy-propionic acid (300 mg, 2.278 mmol) and N-methylmorpholine (341 mg, 3.41 mmol) in anhydrous CH2Cl2 was added drop wise isobutyl chloroformate (457 mg, 3.41 mmol). The resultant mixture was stirred at 25° C. for 1 h. N-(4-((2-aminopyridin-4-yl)oxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (250 mg, 0.578 mmol) was added and the resulting mixture was stirred at 25° C. for 12 h. The reaction mixture was concentrated under reduced pressure to give (S)-1-((4-(2,5-difluoro-4-(1-((4-fluorophenyl)carbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-yl)amino)-1-oxopropan-2-yl acetate (180 mg, 55.9% yield) which was without further purification.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure

Sources & evidence

ORD record: ord-f7584b91d70f4bf2a8f7492d8f810503
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637672B2

Reaction notes

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